Anatomical evidence demonstrating increased plaques and tangles, cell loss and granulovacuolar degeneration in entorhinal cortex, prepiriform cortex, and the anterior olfactory nucleus, regions involved in the processing of olfactory information, suggested functional impairment in olfaction or olfactory-mediated tasks in patients with Alzheimer's Disease (AD). If there is selective early impact on olfaction or in olfactory-mediated tasks in Alzheimer's Disease, then olfactory deficits may aid in diagnosis as well as in understanding the disease. Since memory impairment is one of the earliest symptoms of Alzheimer's Disease, investigation of olfactory memory seems particularly relevant. Using classical psychophysical techniques, this project has demonstrated impaired olfactory threshold sensitivity and odor memory in AD and has related the impaired olfactory sensitivity to the degree of dementia. The project will continue the longitudinal investigation of 100 AD patients and 100 controls in order to follow these subjects through the progression of the disease process. The current proposal seeks to determine the rate of progression of olfactory dysfunction within individuals with AD and to determine the relationship between olfactory impairment and dementia over the course of time in individuals. Proposed experiments will investigate the impact of the disease on additional olfactory tasks which require varying degrees of cognitive function, in order to determine which tasks signal the greatest degree of olfactory impairment at the earliest point in the disease process. The application also proposes to study olfactory function in Down's Syndrome because of its relationship to Alzheimer's disease and because of preliminary data showing olfactory deficits in Down's patients who have reached the age of 30. Individuals with Down's Syndrome of this age typically show plaques and tangles in the brain similar to Alzheimer's patients. With the aim of understanding the development and progression of olfactory dysfunction in Down's Syndrome, the performance of 20 Down's subjects at 10, 15, 20 and 25 yrs. of age, as well as age-matched and mental age- matched controls, on the same battery of olfactory psychophysical tasks given to the Alzheimer's patients will be assessed. Investigating olfactory dysfunction in Alzheimer's disease and in Down's Syndrome has the potential to contribute to diagnostic accuracy and to understanding Alzheimer's disease. The project will also enhance basic understanding of sensory processing in the human olfactory system.